In late-onset cancers (age ≥ 50 years), only mutations in the GNAS and TP53 gene pair are mutually exclusive, while mutations in GNAS and KRAS or TP53 genes, in PIK3CA and APC or KRAS genes, in TP53 and KRAS or SMAD4 genes, and in ATM and SMAD4 genes tend to occur together [13] (Table 1). Here, SMAD4 is linked to cancer.